*Purpose: In patients with Chronic Pancreatitis (CP), specific microRNAs (miRNA) were elevated in circulation before, during islet infusion and after TPIAT. We selected a panel of 12 miRNAs (hsa-miR-375, hsa-miR-29b-3p, hsa-miR-148a-3p, hsa-miR-216a-5p, hsa-miR-7-5p, hsa-miR-221-3p, hsa-miR-320d, hsa-miR-122-5p, hsa-miR-200c-3p, hsa-let-7e-5p, hsa-miR-125b-5p, hsa-miR-99b-5p) for further analysis of associations with fibrosis and metabolic outcomes after TPIAT.

*Methods: Plasma miRNAs (4 time-points: pre-TPIAT, 6 h after islet infusion, 3 months and 1 year after transplantation) were measured using miRCURY LNA SYBR green qPCR assays. Picosirius red staining (PRS) was performed to assess extent of fibrosis on biopsies collected after pancreas procurement during TPIAT. Correlation analyses were performed using R software (Version 4.1.0).

*Results: At 6 h after islet infusion, hsa-miR-375 (islet specific), hsa-miR-216a-5p (acinar cell specific) and hsa-miR-122-5p (liver specific) were significantly elevated (p<0.001) and returned to baseline levels at 3 months post TPIAT. At 3 months and 1 year after TPIAT, circulating levels of other miRNAs were elevated compared to pre-TPIAT levels (p<0.05, p<0.01, p<0.001). PSR stained area (%) was associated inversely with pre-TPIAT hsa-miR-375 (Fig.1A), hsa-miR-221-3p (Fig.1B), hsa-miR-7-5p (Fig.1C), hsa-miR-29b-3p (Fig.1D), and hsa-miR-99b-5p (Fig.1E) measured at 6 h after islet infusion, hsa-miR-7-5p (Fig.1F), hsa-let-7e-5p (Fig.1G), hsa-miR-200c-3p (Fig.1H), hsa-miR-221-3p (Fig.1I), hsa-miR-29b-3p (Fig.1J), and hsa-miR-99b-5p (Fig.1K) measured at 3-months post TPIAT. A subset of circulating miRNAs measured at 6 h after islet infusion were inversely associated with metabolic outcomes (fasting glucose, C-peptide and HbA1c) at 3- and 6-months post TPIAT.

*Conclusions: Inverse relationship was observed between fibrosis, post-transplant function and specific circulating miRNAs in patients undergoing TPIAT.

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